Cutaneous Leishmaniasis (CL) is a worldwide disease that is endemic in 88 countries [1] . It is estimated that 1.5 million people suffer from CL annually and that more than 350 million are at risk of contracting the infection [2-4]. In America, 60,000 new cases of CL are reported annually [5], being endemic in 20 of its 22 countries and in 2 islands of the Caribbean [2]. Currently, CL has affected more than 500 U.S. Army soldiers serving in Iraq [6]. In the Andean region, the incidence of Leishmaniasis has been increasing dramatically over the last two decades; reaching more than 14,000 cases per year from 1996-98 [7]. In Colombia 6,500 cases have been reported [8]. The increase in the reported cases of CL in Colombia has been related to factors such as migration, deforestation, the multiplication of illicit plantations, the armed political conflict and the behavioral changes of the vector. The main strains of Leishmania in Colombia are L. panamensis, L. brazilensis, L. infantum and L. guyanensis, which are distributed throughout the entire national territory, predominantly in the rural areas [10]. CL is caused by intracellular protozoan parasites of the genus Leishmania [1] and is transmitted to humans through the bite of a small percentage of the species of phlebotomus and lutzomyia sandflies classified to date [10]. In the digestive system of the sandflies, this dimorphic parasite presents an extracellular flagellated form called a promastigote, which upon its release in the host blood, is phagocytized by the macrophage, losing its flagella and turning into an amastigote [12]. Dogs, rodents and didelphidae are the natural hosts of the parasite while man is an incidental host [11]. This zoonosis has suffered an interesting urbanization phenomenon, changing from an eminent rural entity affecting mainly men of an active age, to a disease that is affecting all people, especially children [8,9]. The characteristic lesions of this disease are ulcers that heal spontaneously over a period of three months to a year, depending on the isolate, and that leave a flat, atrophic and depigmented scar [13-15]. The CL, especially the one produced by L. brazilensis can evolve into mucocutaneous Leishmaniasis (MCL), which has a worse prognosis owing to the deforming character of its lesions [16]. The spontaneous cure of these lesions allows for the acquisition of partial resistance to reinfection, which could explain the higher pathogenicity observed in the children and young adult population [9]. Previous studies have shown a higher incidence of CL and a poor response to treatment in the children population [17]. The program of epidemiological vigilance in Colombia requires that the probable cases of CL (identified by ulcer features and by the patient's origin) be confirmed by microscopic direct examination of a secession sample obtained from the ulcer, if these are negative, by biopsy of the wound. Once confirmed, the cases must be notified to the Local Health Secretary using clinical-epidemiological records. This institution, in charge of the epidemiological vigilance, studies the sources of transmission and distributes the medication to the people affected. Currently, various aspects are considered when treating CL, among which, the risk of developing MCL, the grade, localization, number, size, evolution and persistence of the lesions, are the most important [18]. For more than 60 years, the pentavalent antimony compounds: sodium stibogluconate, (Pentostan®, produced by Glaxo-Wellcome) and meglumine antimoniate, (Glucantime®, produced by Sanofi-Aventis) have been considered the treatments of choice for this disease [19]. Studies made in Colombia reported a percentage of cure of 85%, using meglumine antimoniate [20,21]. Despite the fact that the efficacy of these drugs is high, they present many disadvantages such as parenteral administration, and, reversible secondary effects such as nausea, vomiting, muscular and abdominal pain, cardiac problems, a rise in the concentration of hepatic aminotransferases, and chemical pancreatitis [21,22]. Additionally, the adherence to the treatment is affected by its duration (several weeks) and its availability by the restriction in its distribution. Therapeutic alternatives of second line have been proposed; amphotericin B and pentamidine have been used with excellent results, nevertheless their high cost, little availability, the necessity to hospitalize the patients for their administration and the severity of their secondary effects have limited their use [23,24]. In the last decade new treatments for CL have been developed, using oral agents such as mefloquine, itraconazole, miltefosine, paromomycin, ketoconazole, allopurinol and dapsone, however, they have not shown enough evidence of their effectiveness [19,21,25,26]. In an effort to develop a topical treatment for CL, paromomycin has been used in different preparations. However, rates of curation achieved with this medication have not been higher than conventional treatments, even when compared with placebo [27,28]. In several studies, in vitro and in vivo, it has been demonstrated that nitric oxide (NO) is effective to eliminate various strains of Leishmania in its amastigote form [29-35]. The production of NO from the oxidation of L-arginine caused by the inducible nitric oxide synthase (iNOS) constitutes one of the most important defense mechanisms of the macrophages [36], in which two oxidative forms of defense against Leishmania have been identified. During the first phase of infection, in response to the phagocytosis process, some promastigotes are eliminated due to the release of the superoxide ion, a process which is catalyzed by the NADPH oxidase [29]. Those promastigotes that survive this defense mechanism evolve into amastigotes, activating the production of IL-12 in the macrophages and promoting the presentation of the antigens of Leishmania [29] to the T helpers 1 lymphocytes that enhance the cytotoxic activities of the macrophages toward the intracellular parasites via the interferon gamma (INFγ) and the tumor necrosis factor alpha (TNFα) by promoting the production of NO catalyzed by iNOS [31-33]. A recent study shows a higher activity of iNOS in the macrophages of subjects infected with CL, suggesting a vital role of NO in the immunological activity against Leishmania [34]. In Studies with rodents resistant to Leishmania infection (C57BL/6), where L. major, L. chagasi or L. donovani were inoculated, the application of iNOS inhibitors like NG-monomethyl-L-arginine (L-NMMA) caused a higher rate of survival and virulence of the parasites in macrophages [33,35,37,38]. After inoculating L. major in mice with the genetic susceptibility to develop infections with Leishmania (BALB/C), no activity of iNOS was observed. However, the application of IL-12, was able to control the infection by activating iNOS [31]. In humans, several clinical trials have been realized with topical treatments containing NO donors [39,40]. In Ecuador, our group developed and tested a NO generating topical cream with S-nitroso-N-acetylpenicillamine (SNAP), evidencing a beneficial effect in the management of this type of ulcers with no reports of any serious adverse event. Nevertheless, due to the unstable nitric oxide release, the cream had to be applied frequently (4 times a day) making the adherence to the treatment difficult [39]. In Syria, another group used potassium nitrate acidified with salicylic acid and ascorbic acid for the topical treatment of L. tropica [40]. In vitro, this NO generating mixture destroyed the amastigotes and promastigotes of Leishmania; however, in vivo, the study of 40 patients presented inconsistent results, reducing the size of the ulcer in 28% of the subjects and healing only 12%. The discrepancy in these results is believed to be due to the technique used to obtain the NO. The acidification of nitrite produces an instant blast of NO, but its release is not maintained over a long period of time [40]. The difficulty of controlling the liberation of NO has created the necessity of looking for new techniques to regulate its release. The nanofiber polymers produced by the electrospinning technique have been studied in order to guarantee the constant release of pharmaceuticals on the lesion. In the electrospinning process, a high voltage is used to create an electrically charged jet of polymer solution, which dries and solidifies to leave behind a dry polymer fiber [41]. As this jet travels through the air, the solvent evaporates leaving behind a charged fiber that can be electrically deflected and collected on a metal screen [42,43]. Fibers with a variety of cross sectional shapes and sizes are produced from different polymers. With this technique, the encapsulation or entrapment of several pharmaceuticals, enzymes and proteins has been successful. In a previous study, nanofiber patches were successfully used as releasing vehicles of tetracycline hydrochloride. The release of tetracycline was constant for a period of 5 days [41;43]. Using the same model, a multilayer transdermal patch has been produced, in which nitrite is bound to an ion exchange resin (DOWEX) and electrospun into a polyurethane nanofibers layer. A solution containing Waterlock® superabsorbent and polyurethane is electrospun on top of the nitrite-DOWEX layer. The ascorbic acid entrapped in the polyurethane solution is electrospun onto a third layer, with another layer of Waterlock® superabsorbent and polyurethane as the fourth and final one. Upon hydration, this Nitric Oxide Releasing Patch (NOP) produces a stable release of 3.5 µmol of NO during 12 hrs [41,44,45]. In a pilot study, developed in Landazuri, Santander, Colombia, a placebo-controlled clinical trial was conducted with 35 patients who presented 68 ulcers produced by L. panamensis. Using the NOP, a 65% improvement was observed in the treated ulcers, with only a 25% improvement in the placebo group (p=0.001). In this pilot study the unique adverse event described was pruritus in the area where the patch was applied (unpublished data). Taking into account the wide distribution of CL, the changes in its form of transmission and the difficulty related with the availability of medication, this study proposes to investigate whether the NO donor transdermal patch, produced by electrospinning is, at least, as effective as the meglumine antimoniate for the treatment of CL, with less adverse events and a lower cost, constituting therefore an effective therapeutic alternative. In case that the effectiveness of the NOP is demonstrated in this study, a novel and safe therapeutic alternative of easy access and higher adherence for one of the most important public health problems in our country will be made available.